Not provided
Not provided
Not provided
Not provided
Not provided
All subjects who were enrolled completed the study. However, the PI left the institution and the study was terminated before all cohorts were enrolled.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The main objectives of the study are to determine peak plasma drug concentration levels and corresponding time of dexmedetomidine following intranasal administration in children age ≥1 mo to ≤ 6 yr with congenital heart disease undergoing an elective diagnostic or interventional cardiac catheterization procedure.
The high anxiety levels that children may experience during the preoperative period may be associated with negative medical, psychological, and social consequences. To reduce this stress, and to facilitate separation from parents and the induction of anesthesia, children are often given a sedative prior to undergoing a procedure. Dexmedetomidine is a highly selective a2-adrenergic receptor agonist with sedative, anxiolytic, and analgesic properties. While off-label in its use, the administration of dexmedetomidine by the intranasal route has become a popular and effective technique for sedation in children because it is non-invasive, easy to administer, well tolerated, and relatively fast in onset. Despite this, little consistent data have been published on its onset time, duration of action, or optimal dose. The only available pharmacokinetic (PK) data on dexmedetomidine in pediatric patients is in children who were administered IV dexmedetomidine. We are proposing a prospective open-label inter-subject cohort dose-escalation pharmacokinetic study to obtain peak dexmedetomidine drug concentration level in plasma and the corresponding time point following intranasal administration in the pediatric patient with cardiac disease.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Cohort 1A:
Cohort 1B:
|
|
| Cohort 2 | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | Dose-escalation of atomized intranasal dexmedetomidine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Samples Obtained Per Subject | Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. This is the number of samples obtained per subject. | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
| Time of Peak Drug Concentration Level of Dexmedetomidine | Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. The time of peak drug concentration will be determined based on this data. | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
| Serum Drug Concentration Levels of Dexmedetomidine | Following administration of atomized intranasal dexmedetomidine, serum samples will be obtained at the following times post administrations: 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. Peak concentration will be determined based on this data. | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
| Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL | Dose-limiting toxicities (DLT) include bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event possibly, probably, or definitely related to intranasal dexmedetomidine administration that occured after the administration of the intranasal dexmedetomidine and through the completion of PK sampling. Bradycardia, hypotension, or new intraventricular conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team as part of usual clinical care were not considered DLTs but were considered an adverse event. Any events that could not be explained by the intervention that the patient was undergoing were assumed to be related to the study drug. |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kelly L Grogan, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19106 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Some of our subjects were scheduled for a cardiac MRI prior to their heart catheterization. If the MRI answered the clinical question, the heart catheterization was not performed and therefore study drug was not administered.
Prospective open-label inter-subject cohort dose escalation PK and PD study performed at a since center in a pediatric cardiac catheterization laboratory. Study was approved by IRB on 4/23/18 and the FDA initiation date was 11/29/17. Subjects were enrolled from 06/14/18 through 8/23/21. All study related activities were completed on 10/13/21.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 2 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 1A:
|
| FG001 | 2 ug/kg; Subjects Age ≥1 mo and ≤2 yo | Cohort 1a:
|
| FG002 | 4 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 2
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 2 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 1A:
|
| BG001 | 2 ug/kg; Subjects Age ≥1 mo and ≤2 yo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Samples Obtained Per Subject | Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. This is the number of samples obtained per subject. | Population includes all subjects who received study drug. This included evaluable and non-evaluable subjects. | Posted | Median | Inter-Quartile Range | Samples | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
|
All subjects were monitored for 6 hours after the administration of study drug.
Drug Limiting Toxicities (DLT) were defined as bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event related to intranasal dexmedetomidine that occurred after the administration of the intranasal drug and through the completion of PK sampling. Bradycardia, hypotension, or new conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team were considered an adverse event but not a DLT.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 1A:
|
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia not requiring intervention | Cardiac disorders | Systematic Assessment | Bradycardia was a defined adverse event. Bradycardia was defined as a HR <80 bpm in subjects < 1 year old and <60 bpm in subjects >1 year old. This was considered a dose limiting toxicity if if occurred after the administration of study drug. |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kelly Grogan | Children's Hospital of Philadelphia | 410-279-6994 | grogank@chop.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 6, 2020 | Sep 28, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 20, 2020 | Sep 28, 2022 | ICF_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Subjects were monitored for 6 hours after the administration of study drug. |
| Met exclusion criteria after obtaining consent |
|
| Inadequate study staff available to process samples |
|
Cohort 1a:
| BG002 | 4 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 2
|
| BG003 | Total | Total of all reporting groups |
| months |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Median | Inter-Quartile Range | kilograms |
|
| Mixing lesion present | Subjects had a variety of cardiac defects, including those with single versus two ventricle physiology. Subjects were defined by whether they had a mixing lesion or not. These are subjects who had a mixing lesion. | Count of Participants | Participants |
|
Cohort 1a:
|
| OG002 | 4 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 2
|
|
|
| Primary | Time of Peak Drug Concentration Level of Dexmedetomidine | Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. The time of peak drug concentration will be determined based on this data. | Analysis population includes subjects who received study drug and had at least 90 minutes of sampling time to ensure that Tmax had been achieved. There was one subject in Cohort 1a who had BLQ for all samples obtained for unknown reasons. This subject's data also not be evaluated. | Posted | Median | Inter-Quartile Range | minutes | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
|
|
|
| Primary | Serum Drug Concentration Levels of Dexmedetomidine | Following administration of atomized intranasal dexmedetomidine, serum samples will be obtained at the following times post administrations: 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. Peak concentration will be determined based on this data. | Analysis population includes subjects who received study drug and had at least 90 minutes of sampling time to ensure that Cmax had been achieved. There was one subject in Cohort 1a who had BLQ for all samples obtained for unknown reasons. This subject's data could also not be evaluated. | Posted | Median | Inter-Quartile Range | pg/mL | Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration |
|
|
|
| Primary | Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL | Dose-limiting toxicities (DLT) include bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event possibly, probably, or definitely related to intranasal dexmedetomidine administration that occured after the administration of the intranasal dexmedetomidine and through the completion of PK sampling. Bradycardia, hypotension, or new intraventricular conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team as part of usual clinical care were not considered DLTs but were considered an adverse event. Any events that could not be explained by the intervention that the patient was undergoing were assumed to be related to the study drug. | Population includes any subject who received study drug | Posted | Number | Events | Subjects were monitored for 6 hours after the administration of study drug. |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 1 |
| 7 |
| EG001 | 2 ug/kg; Subjects Age ≥1 mo and ≤2 yo | Cohort 1a:
| 0 | 5 | 0 | 5 | 2 | 5 |
| EG002 | 4 μg/kg; Subjects Age >2 yo and ≤ 6 yo | Cohort 2
| 0 | 9 | 0 | 9 | 3 | 9 |
|
| Hypotension not requiring intervention | Cardiac disorders | Systematic Assessment | Hypotension is an adverse event. Hypotension is defined as decrease in mean arterial pressure greater than 30% from pressure before administration of study drug. Defined as DLT if occurred after administration of study drug with no other etiology. |
|
| New Intraventricular conduction delay | Cardiac disorders | Systematic Assessment | An adverse event was defined as the development of an intraventricular delay following the administration of study drug. |
|
| Maximum Plasma Concentration | Cardiac disorders | Systematic Assessment | A maximum plasma concentration >1000 pg/dL was considered a dose-limiting adverse event based on prior data which suggested that when concentrations exceeded this value there was an increased incidence of bradycardia and hypotension. |
|
Not provided
Not provided
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |